Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify genetic determinants of susceptibility to S. aureus, and evaluate their function with regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes was found to be significantly associated with susceptibility to S. aureus infection. Of these 422 genes, whole genome transcription profiling identified five genes (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) that were significantly differentially expressed in a) S. aureus -infected susceptible (A/J) vs. resistant (C57BL/6J) mice and b) humans with S. aureus blood stream infection vs. healthy subjects. Three of these genes (Dcaf7, Dusp3, and Psme3) were down-regulated in susceptible vs. resistant mice at both pre- and post-infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3 induced significant increases of cytokine production in S. aureus-challenged RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) through enhancing NF-κB signaling activity. Similar increases in cytokine production and NF-κB activity were also seen in BMDMs from CSS11 (C57BL/6J background with chromosome 11 from A/J), but not C57BL/6J. These findings suggest that Dusp3 and Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a role in human S. aureus infection.

Unnatural History: Ecological Temporality in Post-1945 American Literature

While environmental literary criticism has traditionally focused its attention on the textual representation of specific places, recent ecocritical scholarship has expanded this focus to consider the treatment of time in environmental literature and culture. As environmental scholars, activists, scientists, and artists have noted, one of the major difficulties in grasping the reality and implications of climate change is a limited temporal imagination. In other words, the ability to comprehend and integrate different shapes, scales, and speeds of history is a precondition for ecologically sustainable and socially equitable responses to climate change.

My project examines the role that literary works might play in helping to create such an expanded sense of history. As I show how American writers after 1945 have treated the representation of time and history in relation to environmental questions, I distinguish between two textual subfields of environmental temporality. The first, which I argue is characteristic of mainstream environmentalism, is disjunctive, with abrupt environmental changes separating the past and the present. This subfield contains many canonical works of postwar American environmental writing, including Aldo Leopold’s A Sand County Almanac, Edward Abbey’s Desert Solitaire, Annie Dillard’s Pilgrim at Tinker Creek, and Kim Stanley Robinson’s Science in the Capital trilogy. From treatises on the ancient ecological histories of particular sites to meditations on the speed of climate change, these works evince a preoccupation with environmental time that has not been acknowledged within the spatially oriented field of environmental criticism. However, by positing radical breaks between environmental pasts and environmental futures, they ultimately enervate the political charge of history and elide the human dimensions of environmental change, in terms both of environmental injustice and of possible social responses.

By contrast, the second subfield, which I argue is characteristic of environmental justice, is continuous, showing how historical patterns persist even across social and ecological transformations. I trace this version of environmental thought through a multicultural corpus of novels consisting of Ralph Ellison’s Invisible Man, Ishmael Reed’s Mumbo Jumbo, Helena María Viramontes’ Under the Feet of Jesus, Linda Hogan’s Solar Storms, and Octavia Butler’s Parable of the Sower and Parable of the Talents. Some of these novels do not document specific instances of environmental degradation or environmental injustice and, as a result, have not been critically interpreted as relevant for environmental analysis; others are more explicit in their discussion of environmental issues and are recognized as part of the canon of American environmental literature. However, I demonstrate that, across all of these texts, counterhegemonic understandings of history inform resistance to environmental degradation and exploitation. These texts show that environmental problems cannot be fully understood, nor environmental futures addressed, without recognizing the way that social histories of inequality and environmental histories of extraction continue to structure politics and ecology in the present.

Ultimately, then, the project offers three conclusions. First, it suggests that the second version of environmental temporality holds more value than the first for environmental cultural studies, in that it more compellingly and accurately represents the social implications of environmental issues. Second, it shows that “environmental literature” is most usefully understood not as the literature that explicitly treats environmental issues, but rather as the literature that helps to produce the sense of time that contemporary environmental crises require. Third, it shows how literary works can not only illuminate the relationship between American ideas about nature and social justice, but also operate as a specifically literary form of eco-political activism.

Behavior Genetics and Post Genomics

The science of genetics is undergoing a paradigm shift. Recent discoveries, including the activity of retrotransposons, the extent of copy number variations, somatic and chromosomal mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challenging a series of dogmas concerning the nature of the genome and the relationship between genotype and phenotype. DNA, once held to be the unchanging template of heredity, now appears subject to a good deal of environmental change; considered to be identical in all cells and tissues of the body, there is growing evidence that somatic mosaicism is the normal human condition; and treated as the sole biological agent of heritability, we now know that the epigenome, which regulates gene expressivity, can be inherited via the germline. These developments are particularly significant for behavior genetics for at least three reasons: First, these phenomena appear to be particularly prevalent in the human brain, and likely are involved in much of human behavior; second, they have important implications for the validity of heritability and gene association studies, the methodologies that largely define the discipline of behavior genetics; and third, they appear to play a critical role in development during the perinatal period, and in enabling phenotypic plasticity in offspring in particular. I examine one of the central claims to emerge from the use of heritability studies in the behavioral sciences, the principle of “minimal shared maternal effects,” in light of the growing awareness that the maternal perinatal environment is a critical venue for the exercise of adaptive phenotypic plasticity. This consideration has important implications for both developmental and evolutionary biology

Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.